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The genetic variation in Monocarboxylic acid transporter 2 （MCT2） has functional and clinical relevance with male infertility

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Asian Journal of Andrology 2014年第5期16卷 694-697,I0007页

作者： jinu lee Dong Ryul lee Suman lee Yonsei Institute of Pharmaceutical Sciences College of Pharmacy Yonsei University Incheon Department of Biomedical Science CHA University Seongnam-si Korea

Monocarboxylic acid transporter 2 （MCT2） transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 （＋28201A 〉 G, rs10506398） and 3＇ untranslated region （UTR） single nucleotide polymorphism （SNP）（＋2626G 〉 A, rs10506399） of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility （n = 471, P 〈 0.05）. In particular, the MCT2-3＇ UTR SNP （＋2626 G 〉 A） had a strong association with the oligoasthenoteratozoospermia （OAT） group. The ＋2626GG type had an almost 2.4-fold higher sperm count than that of the ＋2626AA type （＋2626GG; 66 x 106 vs ＋2626AA; 27 x 106, P 〈 0.0001）. The MCT2-3＇ UTR SNP may be important for expression, as it is located at the MCT2 3＇ UTR. The average MCT2 protein amount in sperm of the ＋2626GG type was about two times higher than that of the ＋2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.

关键词： 3' UTR male infertility monocarboxylic acid transporter 2 single nucleotide polymorphism sperm

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PDTC inhibits NF - κB activation by inhibiting proteasome activity through the mediation of zinc

PDTC inhibits NF - κB activation by inhibiting proteasome a...

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中国药理学会第八次全国代表大会

作者： Chul Hoon KIM In Sook KIM jinu lee Shin Young KANG Joo Hee KIM Hyun Soo KIM Young Soo AHNBrain Korea 21 Project for Medical Sciences Brain Research Institute and Department of PharmacologyYonsei University College of Medicine Seoul 120 - 752 Korea

Pyrrolidine dithiocarbamate (PDTC) is a potent inhibitor of nuclear factor kappa B (NF-κB).We have previously reported that the effects of pyrrolidine dithiocarbamate (PDTC) on cell death and NF-κB inhibition are zinc dependent (Kim et al,FEBS Lett.449, 28-32,1999, Kim,et al,J. Neurochem.72, 1586-1592,1999),not through its antioxidant *** the present study, we sought to characterize the molecular mechanism of PDTC inhibition of NF-κB

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PDTC inhibits NF-□B activation by inhibiting proteasome activity through the mediation of zinc

PDTC inhibits NF-□B activation by inhibiting proteasome act...

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中国药理学会第八次全国代表大会暨全国药理学术会议

作者： Chul Hoon KIM In Sook KIM jinu lee Shin Young KANG JooHeeKIM Hyun Soo KIM Young Soo AHN Brain Korea 21 Project for Medical Sciences Brain Research Institute and Department of Pharmacology Yonsei University College of Medicine Seoul 120-752 Korea

Pyrrolidine dithiocarbamate (PDTC) is a potent inhibitor of nuclear factor kappa B (NF-□B). Wehave previously reported that the effects of pyrrolidine dithiocarbamate(PDTC) on cell death andNF-□B inhibition are zinc dependent(Kim et al, FEBS Lett. 449, 28-32, 1999, Kim, et al, ***. 72, 1586-1592, 1999), not through its antioxidant effect. In the present study, wesought to characterize the molecular mechanism of PDTC inhibition of NF-□B activity. PDTC didnot alter NF-□B binding to DNA, bat prevented the translocation of the p65 subunit of NF-□Binto the nucleus. As an inhibitor of NF-□B, PDTC paradoxically activated I□B kinase (IKK).But, degradation of phosphorylated I□B□was blocked by PDTC. PDTC also stabilized andincreased p53 and p21 proteins that are degraded by proteasome. A highly specific proteasome

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